Nail abnormalities identified in an ageing study of 30 inbred mouse strains

Mustonen, Allison; Silva, Kathleen A.; Kennedy, Victoria E.; Sundberg, Beth A.; Bechtold, Lesley; Alghamdi, Sarah M.; Hoehndorf, Robert; Schofield, Paul N.; Sundberg, John P.

doi:10.1111/exd.13759

Cited by 8 publications

(8 citation statements)

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“…Laminitis results in epidermal pathologies that include abnormal hyperplastic and acanthotic epidermal tissue [19], epidermal dysplasia and metaplasia, loss of cell adhesion, apoptosis, and necrosis [20], and expression of cellular stress, activation, and altered differentiation markers [29;47–49]. Similar nail abnormalities involving the nail bed were recently described in association with ageing in several inbred strains of mice [41]. Our anti-K124 mAbs will be useful for the investigation of histopathological changes in lamellar and nail bed keratin expression and as a tissue-specific differentiation marker for in vitro studies.…”

Section: Discussionmentioning

confidence: 86%

“…Murine Krt42 is expressed in the nail matrix [27], but the equine lamellar-restricted keratins are not expressed in the homologous coronary region of the hoof wall, as assessed by RT-PCR for KRT42 (Fig 2) and multiple methods for KRT124 /K124 (Figs 2–6). The isoform-specific anti-K124 mAbs described here may allow protein localization and tissue distribution of K124/K90 in other species, possibly including studies of murine models of nail disease [41] and comparative evolutionary-developmental biology [25;42].…”

Section: Discussionmentioning

confidence: 99%

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The expression of equine keratins K42 and K124 is restricted to the hoof epidermal lamellae of Equus caballus

et al. 2019

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The equine hoof inner epithelium is folded into primary and secondary epidermal lamellae which increase the dermo-epidermal junction surface area of the hoof and can be affected by laminitis, a common disease of equids. Two keratin proteins (K), K42 and K124, are the most abundant keratins in the hoof lamellar tissue of Equus caballus. We hypothesize that these keratins are lamellar tissue-specific and could serve as differentiation- and disease-specific markers. Our objective was to characterize the expression of K42 and K124 in equine stratified epithelia and to generate monoclonal antibodies against K42 and K124. By RT-PCR analysis, keratin gene (KRT) KRT42 and KRT124 expression was present in lamellar tissue, but not cornea, haired skin, or hoof coronet. In situ hybridization studies showed that KRT124 localized to the suprabasal and, to a lesser extent, basal cells of the lamellae, was absent from haired skin and hoof coronet, and abruptly transitions from KRT124-negative coronet to KRT124-positive proximal lamellae. A monoclonal antibody generated against full-length recombinant equine K42 detected a lamellar keratin of the appropriate size, but also cross-reacted with other epidermal keratins. Three monoclonal antibodies generated against N- and C-terminal K124 peptides detected a band of the appropriate size in lamellar tissue and did not cross-react with proteins from haired skin, corneal limbus, hoof coronet, tongue, glabrous skin, oral mucosa, or chestnut on immunoblots. K124 localized to lamellar cells by indirect immunofluorescence. This is the first study to demonstrate the localization and expression of a hoof lamellar-specific keratin, K124, and to validate anti-K124 monoclonal antibodies.

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

The expression of equine keratins K42 and K124 is restricted to the hoof epidermal lamellae of Equus caballus

et al. 2019

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“…Laminitis results in epidermal pathologies that include abnormal hyperplastic and acanthotic epidermal tissue [37], epidermal dysplasia and metaplasia, loss of cell adhesion, apoptosis, and necrosis[27], and expression of cellular stress, activation, and altered differentiation markers [24;38-40]. Similar nail abnormalities involving the nail bed were recently described in association with ageing in several inbred strains of mice [41]. Our anti-K124 mAbs will be useful for the investigation of histopathological changes in lamellar and nail bed keratin expression and as a tissue-specific differentiation marker for in vitro studies.…”

Section: Discussionmentioning

confidence: 88%

The expression of equine keratins K42 and K124 is restricted to the hoof epidermal lamellae ofEquus caballus

Armstrong

Cassimeris

Santos

et al. 2019

Preprint

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HGH)2 29 Abstract 30 The equine hoof inner epithelium is folded into primary and secondary epidermal lamellae which 31 increase the dermo-epidermal junction surface area of the hoof and can be affected by laminitis, 32 a common disease of equids. Two keratin proteins (K), K42 and K124, are the most abundant 33 keratins in the hoof lamellar tissue of Equus caballus. We hypothesize that these keratins are 34 lamellar tissue-specific and could serve as differentiation-and disease-specific markers. Our 35 objective was to characterize the expression of K42 and K124 in equine stratified epithelia and to 36 generate monoclonal antibodies against K42 and K124. By RT-PCR analysis, keratin gene (KRT) 37 KRT42 and KRT124 expression was present in lamellar tissue, but not cornea, haired skin, or 38 hoof coronet. In situ hybridization studies showed that KRT124 localized to the suprabasal and, 39 to a lesser extent, basal cells of the lamellae, was absent from haired skin and hoof coronet, and 40 abruptly transitions from KRT124-negative coronet to KRT124-positive proximal lamellae. A 41 monoclonal antibody generated against full-length recombinant equine K42 detected a lamellar 42 keratin of the appropriate size, but also cross-reacted with other epidermal keratins. Three 43 monoclonal antibodies generated against N-and C-terminal K124 peptides detected a band of the 44 appropriate size in lamellar tissue and did not cross-react with proteins from haired skin, corneal 45 limbus, hoof coronet, tongue, glabrous skin, oral mucosa, or chestnut on immunoblots. K124 46 localized to lamellar cells by indirect immunofluorescence. This is the first study to demonstrate 47 the localization and expression of a hoof lamellar-specific keratin, K124, and to validate anti-48 K124 monoclonal antibodies. 3 49 1. Introduction 50 The skin and its appendages are made of stratified epithelia composed of keratinocytes, 51 defined by expression of keratin intermediate filament proteins (abbreviated K for proteins and 52 KRT for genes) [1]. Keratin filaments resist stretching (strain) and provide tensile strength to 53 epithelia and skin appendages. Tissue-and differentiation-specific variation in specific keratin 54 isoform content determines the physical and mechanical properties of diverse epithelial tissues 55 and of their keratinocyte building blocks [2;3]. Understanding how keratins function to provide 56 mechanical stability is crucial to our understanding of human diseases associated with keratin 57 mutations and abnormal keratin expression [4-8]. Here we describe unique keratins of the equine 58 (Equus caballus) epidermal lamellae, a highly specialized tissue that withstands extreme force 59 and provides a model for understanding how keratins provide mechanical strength to flexible 60 tissues. 61 Each single-toed foot of a 500 kg horse (E. caballus) must withstand peak ground reaction 62 forces of 2-5,000 N while protecting the underlying limb from trauma [9;10]. The equine 63 adaptation to single-toed unguligrade locomotion requires the ...

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“…Ezhkova's group comprehensively compared the embryonic origin and signalling aspects of Merkel cell specification in hairless paw vs haired dorsal skin and reports on the regional differences . Sundberg et al preformed a large‐scale ageing phenotype screen of nail abnormalities across common inbred mouse strains and reveal previously unappreciated genotype‐dependent nail defect associations. Related to skin pigmentation, Watt's group implicates the myosin superfamily member MYO10 in regulating normal bodywide pigment pattern formation, while a review article comprehensively discusses the broader aspects of melanocyte lineage biology, including during skin development …”

Section: Skin Morphogenesis Across the Developmental Levelmentioning

confidence: 99%

Understanding skin morphogenesis across developmental, regenerative and evolutionary levels

Plikus

Chuong

2019

Experimental Dermatology

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Nail abnormalities identified in an ageing study of 30 inbred mouse strains

Cited by 8 publications

References 37 publications

The expression of equine keratins K42 and K124 is restricted to the hoof epidermal lamellae of Equus caballus

The expression of equine keratins K42 and K124 is restricted to the hoof epidermal lamellae of Equus caballus

The expression of equine keratins K42 and K124 is restricted to the hoof epidermal lamellae ofEquus caballus

Understanding skin morphogenesis across developmental, regenerative and evolutionary levels

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